Thyrotropin and thyroglobulin as an index of optimal iodine intake: correlation with iodine excretion of 39,913 euthyroid patients.

The recommendations for the dietary allowance of iodine are 150 micrograms per day for adolescents and adults. Thyrotropin (TSH) and thyroglobulin (Tg) can be used as surveillance indicators for assessing iodine deficiency disorders. We compared the relation between TSH and Tg, free triiodothyronine, and thyroxine serum levels with urinary iodine excretion in 2311 untreated euthyroid patients using our modified cericarsenite method. An adequate iodine intake may be assumed when TSH and Tg values are at the lower end of the normal range. Patients were grouped according to urinary iodine excretion and goiter size. In the group with an iodine excretion between 201 and 300 micrograms of iodine per gram of creatinine, the lowest TSH values and even low Tg levels could be shown. We conclude that an iodine intake of approximately 250 micrograms/day is associated with the lowest TSH stimulation to thyrocytes. In the groups separated according to thyroid size, significantly higher Tg levels were found in the patients with uninodular and multinodular goiter as a result of longstanding iodine deficiency, whereas actual urinary iodine excretion did not differ significantly. Additionally, iodine excretion of 39,913 euthyroid patients between 1984 was 1996 was examined. In Austria iodized salt (10 mg KI/kg) was introduced by law in 1963 and increased to 20 mg KI/kg salt in 1990. An initial increase of iodine excretion until 1993 was followed by a decrease in 1994 and 1995 without further changes in 1996. These results show that iodine intake has improved since 1984; however, in 1996 iodine excretion in one-third of the investigated patients was under 100 micrograms per gram of creatinine and more than 80% had less than 200 micrograms per gram of creatinine.

Methimazole has no dose-related effect on the intensity of the intrathyroidal autoimmune process in relapsing Graves' disease.

Declining thyroid autoantibodies during treatment and decreased lymphocytic infiltration after treatment of patients with Graves' disease suggest immunosuppressive actions of antithyroid drugs. However, the recent report of similar relapse rates after low and high dose carbimazole treatment of Graves' disease seems to contradict the immunosuppression thesis. We therefore determined the intrathyroidal methimazole concentrations with a high performance liquid chromatography method in 17 patients undergoing subtotal thyroid resection for relapsing Graves' disease. The intensity of the intrathyroidal infiltration by immunoglobulin G-producing plasma cells, activated T cells, and antigen presenting cells, and the total number of lymphocytes were identified immunohistologically with monoclonal antibodies for kappa- and lambda-immunoglobulin light chains, UCHL1, and the S100 antibody, respectively, followed by morphometry. The intrathyroidal methimazole concentration and the cumulative preoperative methimazole doses did not correlate with the intensity of the intrathyroidal infiltration by any of these immunocompetent cells. Comparison of groups with significantly different intrathyroidal methimazole concentrations (134 ng/g, n = 8 vs. 993 ng/g, n = 7) showed no significant differences for any of the intrathyroidal immunocompetent cells. These findings suggest that there is no dose-related effect of methimazole on the intensity of the intrathyroidal autoimmune process of patients with relapsing Graves' disease. They provide an explanation for why it does not seem justifiable to recommend higher methimazole doses than those required for the control of hyperthyroidism with the goal of immunosuppression.

[Familial dysalbuminemic hyperthyroxinemia in long-term amiodarone treated patients]. / Familiäres dysalbuminämisches Hyperthyroxinämie-syndrom unter Amiodaron-Langzeitbehandlung.

A serum sample of an outpatient, under long-term amiodarone (AM) treatment was submitted for routine checkup of thyroid function parameters. It revealed the pattern of euthyroid dysalbuminemic hyperthyroxinemia. Since no results have been published so far covering the influence of amiodarone on the specific thyroxine binding proteins, we undertook a prospective study to investigate 28 amiodarone patients, comparing these with a series of age and sex matched euthyroid subjects. Not one amiodarone patient showed changed radio-T4 distribution against the normal group. Yet, in 3 relatives of the propositus, familial screening revealed the typical pattern of thyroid function tests and of T4 distribution in radio immune ice gel electrophoresis, respectively, proving familial dysalbuminemic hyperthyroxinemia syndrome. Thus, it is most likely that this syndrome has been prevalent already prior to the amiodarone administration and consequently amiodarone was of no influence on thyroxine transport protein patterns.

The influence of iodine on the intensity of the intrathyroidal autoimmune process in Graves' disease.

Several lines of evidence support an etiological role of iodine for the initiation and perpetuation of autoimmune thyroid disease. However, varying relapse rates after increased iodine supplementation have been reported for Graves' disease. Furthermore the effects of iodine on the intensity of human autoimmune thyroiditis have previously only been investigated by indirect parameters and actions of iodine on thyroid function and a possible enhancement of the intrathyroidal autoimmune process in Graves' disease are difficult to separate in previous studies. Moreover lymphocytic thyroiditis in animal models has always been induced by considerably higher iodine doses as those used in in vivo studies. Therefore we investigated the effect of low and high iodine concentrations on the intensity of the intrathyroidal autoimmune process in Graves' disease. The intensity of intrathyroidal infiltration by lymphocytes, memory T cells, plasma cells and antigen presenting cells was determined by quantitative immunohistologic methods in 38 Graves' disease patients. 12 patients received additional preoperative iodine (group II) and 26 were treated with thiourelene antithyroid drugs only (group I). Urinary and intrathyroidal iodine concentrations were determined by a modified cer arsenite method in both groups. Application of high iodine doses in group II induced a significant increase of kappa and lambda positive plasma cells and interdigitating reticulum cells. This was not observed for activated T cells. There was no correlation between the extent of intrathyroidal infiltration by activated T cells, plasma cells and antigen presenting cells, and intrathyroidal or urinary iodine or intrathyroidal iodine concentrations in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Simple determination of iodine in small specimens of thyroid tissue.

This work describes a simple photometric determination of the iodine concentration in thyroid tissue, a method based on the well-known catalytic Sandell-Kolthoff reaction. The modified ceric arsenite reaction is very sensitive and does not require complicated laboratory equipment. It can be performed in any routine clinical laboratory if instructions are followed strictly. By means of this method iodine concentration can be determined even in small specimens, for instance puncture samples of thyroid tissue or thyroid glands of small animals (mouse). Previous to the analysis, the tissue is digested in a mixture of sodium chlorate and perchloric acid at 100 degrees C. Using this manner of digestion between 94 and 110% of iodine in the sample were recovered. Comparison with neutron activation analysis showed excellent agreement of the obtained values.

[Evaluating thyroid gland function in patients with protein anomalies]. / Beurteilung der Schilddrüsenfunktion bei Patienten mit Proteinanomalien.

The euthyroid hyperthyroxinemia (EHT) is characterized on the one hand by a normal basal THS or TRH-TSH response but also by high plasma values of total thyroxine (TT4) on the other. However if only TT4 is assessed, "hyperthyroidism" may be diagnosed erroneously. EHT may be caused by an increase of specific thyroxine binding proteins which may be hereditary (permanent) or acquired (transient). The most frequent disturbance is due to an estrogen induced increase of thyroxine binding globulin (TBG) in the course of pregnancy, anticonceptive drugs or estrogen treatment. The albumin associated HT (FDH syndrome), first reported in 1979, has autosomal dominant traits. 144 patients with FDH syndrome were observed during the period between 1984 and 1990, i.e. 7% (1986) of all hyperthyroid patients explored. Family screening is required to prevent unjustified treatment. Additionally existing disturbances of thyroid function as well as other protein binding anomalies may both cause problems in differential diagnosis. Prealbumin associated hyperthyroxinemia (PAAH), first published in 1982, may be due to an inherited increase in affinity, but may also be the consequence of a true elevation of prealbumin plasma concentration in the course of an islet cell cancer; both conditions are extremely rare. Nearly as rare are patients with plasma autoantibodies directed against T4 and/or T3 (5 cases); yet, a reverse T3 autoantibody could be observed in merely 1 case. By means of our modified radio-thyroxine-agarosegel-iceelectrophoresis all such protein anomalies may be diagnosed and differentiated in 1 procedure. Moreover, all other types of EHT must be taken into consideration by differential diagnosis.

[Iodine supplementation in the province of Styria]. / Zur Jodversorgung in der Steiermark.

As far back as 1898 the Austrian Nobel price winner Wagner von Jauregg was the first to recommend iodination of salt as prophylaxis against endemic goitre (prevalence 48%) and cretinism (greater than 10%). In 1923 he achieved in a voluntary iodine supplementation of 5 mg KJ/kg table salt, which only lasted for a number of years. It was in 1963 when finally a mandatory iodized salt prophylaxis was introduced at the rate of 10 mg KJ/kg. In this study the effect of 25 years of iodine supplementation is investigated: Endemic cretinism, hypothyroidism, and goitre in newborns disappeared generally and endemic goitre in pupils was significantly reduced. However, due to epidemiological studies at elementary and secondary schools and army recruitment examinations we still found out endemic goitre grade I (according to WHO) mainly in female juveniles. Examinations were done by palpation, ultrasonography and urinary iodine excretion. In the above as well as in the urine of newborns and in mother's milk the iodine content was significantly lower than in iodine rich countries. Consequently a higher iodination of salt at the rate of 20 mg KJ/kg was recommended by the Austrian Society of Nuclear Medicine in 1985. This suggestion was taken up by the Austrian authorities and it will finally be instituted by law in May 1990 for the benefit of coming generations.

Serum selenium levels in distinct manifestations of coronary artery disease.

The trace element selenium plays an important role in the oxidation of lipids and is therefore closely associated with atherosclerosis. In a series of 49 unselected male patients having undergone coronary angiography, the serum selenium level was determined using flameless atomic absorption spectrometry (Zeeman technique), and compared to a standard (Seronorm; Nycomed). In the whole series the serum selenium levels were markedly decreased with no significant difference between patients with or without coronary artery disease. The severity of the coronary artery disease (CAD) did not correlate with the selenium level. However, patients with prior myocardial infarction had a significant higher selenium level than those without. Thus, the level of selenium does not appear to be a marker or a risk factor for coronary artery disease.

[Changes in zinc level in the serum, whole blood and erythrocytes in disorders of thyroid function]. / Veränderungen des Zinkspiegels im Serum, Vollblut und im Erythrozyten bei Schilddrüsen-Stoffwechselstörungen.

The zinc level in serum and whole blood was determined in a series of 121 patients, 20 suffering from overt hyperthyroidism, 34 with manifest hypothyroidism and a control group of 67 euthyroid subjects. The zinc content per deciliter of erythrocytes was calculated from the haematocrit. The hyperthyroid group revealed a highly significantly elevated serum zinc level (p less than 0.01), but a most significantly reduced zinc content in whole blood (p less than 0.001) in comparison with the euthyroid group. On the other hand, the reverse changes were observed in the hypothyroid group, i.e. a most significantly reduced serum zinc content (p less than 0.001) and a highly significantly increased zinc content in whole blood (p less than 0.01). These results suggest that the determination of zinc levels both in serum and in whole blood may be a useful additional parameter of peripheral thyroid hormone effect.

[Method for the determination of protein binding of thyroid gland hormones and the detection of antibodies to T4 and T3]. / Methode zur Bestimmung der Proteinbindung der Schilddrüsenhormone und zum Nachweis von Antikörpern gegen T4 und T3.

More than 99% of circulating thyroid hormones are bound with defined capacity and affinity to transport proteins such as thyroxine binding globulin, albumin and prealbumin. Variants of albumin and/or prealbumin, often familial, will bind T4 and sometimes T3 with increased affinity causing higher TT4 and TT3 values respectively. In determining fT4 and fT3 by analogue tracer its binding to protein variants will also lead to falsely raised free parameters. Thus the possibility of a false diagnosis of hyperthyroidism arises. Also the presence of T4 and T3 autoantibodies will cause misleading findings of increased thyroid hormone parameters as against euthyroid metabolism. For determining the pattern of T4 and T3 protein binding as well as autoantibodies radioactive labelled T4 or T3 is incubated with the patients serum. Transport proteins are separated by means of horizontal agarose gel electrophoresis with water cooling. The gel is sectioned and the activity of individual gel particles is measured in a Gammacounter. The activity graph shows with high precision the binding pattern of T4 and T3 to transport proteins. Moreover, this method also serves to determine any possible T4 and T3 autoantibodies, indicated by a peak in the activity graph in the gamma globulin range.

Radioelectrophoresis for determination of thyroid hormone binding abnormalities in human serum.

This paper describes a rapid and accurate method for determining binding abilities of thyroid hormones to their corresponding serum proteins: prealbumin, albumin and thyroxine binding globulin. A tube cell agarose gel electrophoresis is used with radioactive labelled triiodothyronine or thyroxine. The distribution curve shows characteristic peaks for prealbumin, albumin and thyroxine binding globulin. A collective of 60 euthyroid thyroid-healthy persons was examined, and the following reference values for the binding of thyroxine to its binding proteins were found: The percentage binding of thyroxine to the prealbumin fraction is 21 to 33%, to the albumin fraction 10 to 15% and to the thyroxine binding globulin fraction 54 to 66%. In a group of 220 patients with suspected thyroid hormone binding abnormalities there were 42 cases of albumin-associated hyperthyroxinaemia, 5 cases of prealbumin-associated hyperthyroxinaemia and 2 cases of thyroxine binding globulin deficiency. In another group of 35 patients with suspected antibodies against thyroid hormones one patient showed antibodies against triiodothyronine.

[Detection of thyroid hormone antibodies using a radial immunodiffusion method]. / Nachweis von Schilddrüsenhormonantikörpern mittels einer radialen Immundiffusionsmethode.

T3 and T4 autoantibodies just as protein binding anomalies are the cause of discrepancies of thyroid hormone assays as against actual thyroid function. Depending on the separation techniques used, autoantibodies lead to false low or high T3 or T4 values. A series of 105 preselected thyroid patients was investigated as to the presence of T3 and T4 autoantibodies. Only in one of these patients T3 autoantibodies could be documented as cause for elevated fT3 values in otherwise euthyroid function (clinically euthyroid, positive TRH/TSH response, euthyroid peripheral tissue parameters). The remaining 104 subjects showed neither T4 nor T3 autoantibodies. The method of investigation developed for final diagnosis of T4 and T3 autoantibodies was done by a radial immune diffusion technique. Here the serum sample was incubated for 12 hours at room temperature with radioactive labelled T3 or T4, then applied on to an antiIgG immune diffusion disc. The radioactivity of the punched precipitation area is measured. This method is quick and easily carried out and highly suitable as screening method.

Chromium content of normal and pathologically altered lung tissue.

Flameless atomic absorption spectrophotometry was used to determine the chromium (Cr) content of samples taken at autopsy from the lungs, bronchi, and regional hilar lymph nodes of 50 randomly selected patients from urban and rural areas; these patients were not known to have been excessively exposed to Cr.On the average, the Cr concentration in the lungs of patients younger than 40 yr of age was approximately 2 µg/g; for patients over 40, the average Cr values were between 5 and 15 µg/g dry wt. The highest values were found in samples from the apex of the lung. The Cr concentration in lung and lymph nodes increased in proportion to age and the degree of anthracosis. Chromium content in the bronchial wall was very low in all cases. Chromium values up to ten times greater as compared to age-matched average values were found in scarred lung tissue, probably caused by a postinflammatory lymph vessel blockade. Slightly elevated Cr values were found in smokers' lungs. Chromium values in tissue from primary lung carcinomas (n=9) were lower than those in neighboring lung tissue. Based on the results of this study the amount of Cr of lung and bronchial tissue does not appear to be associated with the induction of bronchial carcinoma.

[Prealbumin-associated hyperthyroxinemia]. / Präalbuminassoziierte Hyperthyroxinämie.

Prealbumin associated hyperthyroxinaemia represents a rare but important protein binding anomaly, causing difficulties in differential diagnostics. This anomaly is based on a variant prealbumin showing an increased affinity to T4 and rT3 and in some cases also when using T4 analogue tracers. The condition of the patient is clinically euthyroid which is confirmed by a normal bTSH level, a normal response to TRH, and peripheral parameters (BMR, ASR, STI, SHBG) in the euthyroid range. This paper describes the diagnostic difficulties in a 45-year-old male pointing out the significance of precise laboratory determination of prealbumin associated hyperthyroxinaemia in order to avoid misdiagnosis and wrong treatment.

[Urinary excretion of iodide and incidence of goiter in Styria--studies 20 years after the introduction of compulsory iodinated salt prophylaxis]. / Harnjodidausscheidung und Strumahäufigkeit in der Steiermark--Untersuchungen 20 Jahre nach gesetzlicher Einführung der Jodsalzprophylaxe.

20 years after introduction of iodized salt prophylaxis by law in Austria the iodine supply of 6 to 19 year-old school children in Styria was examined. In this study we compared the goitre incidence and urine iodine excretion in children from regions with low iodine intake (locations Graz and Oberwölz) with those of an area where iodine supply was augmented by drinking local iodine containing mineral water (area of Sicheldorf). A modified ceric ion arsenate method was applied for determining urinary iodine excretion. Both in the city of Graz and the rural locality of Oberwölz there still exists an iodine deficiency, grade I (Urine iodine excretion of 50 and 65 micrograms I/g Cr respectively). The goitre incidence in 6 to 10 year olds in Graz amounted to only 4%, while Oberwölz records 8%. This figure in juveniles was relatively high already with 12% in Graz and 15% in Oberwölz. The age group of 15 to 19 years at the Graz secondary school showed a goitre incidence of 12%. The results of the 6 to 10 year olds in the Sicheldorf area recorded a goitre incidence of 4%. Urinary iodine excretion in Sicheldorf: 132,64 micrograms J/g Kre.

[Vitamin A and carotene in thyroid diseases]. / Vitamin A und Carotin bei Schilddrüsenkrankheiten.

From 190 goitrous patients (106 euthyroid, 53 hyperthyroid, 31 hypothyroid) serum levels of vitamin A and carotene were obtained. The serum levels of vitamin A were significantly decreased in both hyperthyroidism and hypothyroidism, the serum levels of carotene in hypothyroidism only. Remarkably, vitamin A levels almost never drop to subnormal values in hyperthyroidism. There is evidence, that a sufficient dietary protein supply enables the liver cell to produce enough amounts of retinol binding protein and prealbumin to overcome the increased clearance observed in hyperthyroid conditions.

[Determination of copper in liver puncture samples in the diagnosis of Wilson's disease]. / Bestimmung von Kupfer in Leberpunktaten zur Diagnose des Morbus Wilson.

Wilson's disease, a hereditary disorder of copper metabolism, is characterized by excessive storage of this metal in several organs. Storage of copper in liver tissue is of great importance in diagnosis and therapy. By means of the combination of two methods - low-temperature ashing and flameless atomic absorption - the copper determination can be made even in smallest liver samples (needle-biopsy samples). It is therefore possible to perform a histological examination, as well as a quantitative copper determination on one puncture sample.